Sex differences in the associations of HDL particle concentration and cholesterol efflux capacity with incident...

Area of Science:

• Cardiovascular Disease Research
• Metabolic Disorders
• Sex Differences in Health

Background:

• Type 1 diabetes (T1D) erodes women's relative protection against coronary artery disease (CAD) compared to men.
• High-density lipoprotein cholesterol (HDL-C) shows a weaker association with reduced CAD risk in women with T1D.

Purpose of the Study:

• To investigate if sex differences in high-density lipoprotein particle concentration (HDL-P) and cholesterol efflux capacity (CEC) explain the altered CAD risk in T1D.
• To compare HDL-P and CEC associations with CAD incidence between men and women with T1D.

Main Methods:

• Quantified HDL-P and CEC (total and ATP binding cassette transporter A1-specific) using calibrated differential ion mobility analysis.
• Assessed clinical CAD events (death, myocardial infarction, revascularization) over a median 26-year follow-up in 550 individuals with T1D.
• Employed multivariable Cox models stratified by sex to analyze HDL-P and CEC associations with CAD incidence.

Main Results:

• Women had higher large HDL-P and lower small HDL-P and ABCA1-specific CEC than men; other measures showed no sex differences.
• HDL-P was negatively associated with CAD incidence in both sexes, but the association was significantly stronger in men, especially for extra-small HDL-P.
• Cholesterol efflux capacity (CEC) did not independently predict CAD in either sex.

Conclusions:

• The association between HDL-P and CAD risk is weaker in women with T1D, particularly concerning extra-small HDL-P.
• HDL-P may be less effective in providing atheroprotection in women with T1D.
• This sex-specific difference in HDL-P's atheroprotective role may explain the absence of a sex difference in CAD incidence in type 1 diabetes.